RT Journal Article
T1 Engraftment characterization of risk-stratified AML in NSGS mice
A1 Díaz de la Guardia, Rafael
A1 Anguita Mandly, Eduardo Luis
A1 Menéndez, Pablo
AB Acute myeloid leukemia (AML) is the most common acute leukemia in adults. Disease heterogeneity is well documented, and patient stratification determines treatment decisions. Patient-derived xenografts (PDXs) from risk-stratified AML are crucial for studying AML biology and testing novel therapeutics. Despite recent advances in PDX modeling of AML, reproducible engraftment of human AML is primarily limited to high-risk (HR) cases, with inconsistent or very protracted engraftment observed for favorable-risk (FR) and intermediate-risk (IR) patients. We used NSGS mice to characterize the engraftment robustness/kinetics of 28 AML patient samples grouped according to molecular/cytogenetic classification and assessed whether the orthotopic coadministration of patient-matched bone marrow mesenchymal stromal cells (BM MSCs) improves AML engraftment. PDX event-free survival correlated well with the predictable prognosis of risk-stratified AML patients. The majority (85-94%) of the mice were engrafted in bone marrow (BM) independently of the risk group, although HR AML patients showed engraftment levels that were significantly superior to those of FR or IR AML patients. Importantly, the engraftment levels observed in NSGS mice by week 6 remained stable over time. Serial transplantation and long-term culture-initiating cell (LTC-IC) assays revealed long-term engraftment limited to HR AML patients, fitter leukemia-initiating cells (LICs) in HR AML samples, and the presence of AML LICs in the CD34− leukemic fraction, regardless of the risk group. Finally, orthotopic coadministration of patient-matched BM MSCs and AML cells was dispensable for BM engraftment levels but favored peripheralization of engrafted AML cells. This comprehensive characterization of human AML engraftment in NSGS mice offers a valuable platform for in vivo testing of targeted therapies in risk-stratified AML patient samples.
PB American Society of Hematology
SN 2473-9529
SN 2473-9537
YR 2021
FD 2021-11-24
LK https://hdl.handle.net/20.500.14352/95483
UL https://hdl.handle.net/20.500.14352/95483
LA eng
NO Díaz de la Guardia R, Velasco-Hernandez T, Gutiérrez-Agüera F, Roca-Ho H, Molina O, Nombela-Arrieta C, Bataller A, Fuster JL, Anguita E, Vives S, Zamora L, Nomdedeu J, Gómez-Casares MT, Ramírez-Orellana M, Lapillonne H, Ramos-Mejia V, Rodríguez-Manzaneque JC, Bueno C, Lopez-Millan B, Menéndez P. Engraftment characterization of risk-stratified AML in NSGS mice. Blood Adv. 2021 Dec 14;5(23):4842-4854.
NO Fundación Hay Esperanza
NO Ministerio de Economía y Competitividad
NO Obra Social La Caixa
NO Interreg V-A programme
NO Health Canada
NO Deutsche Josep Carreras Leukämie Stiftung
DS Docta Complutense
RD 7 abr 2025